Products extracted from a plant of the genus Commiphora, particularly the Commiphora mukul plant, extracts containing same and applications thereof, for example in cosmetics

ABSTRACT

Extracts of the plant Commiphora mukul are used as pigmenting agents and melanocyte culture agents, and for the manufacture of cosmetic and pharmaceutical compositions. Particularly preferred are extracts of the formula IIa, designated Commipherol, and abstracts of the formula IIb designated Commipherin.

BACKGROUND OF THE INVENTION

The invention relates to the use in cosmetics of extracts of a plant ofthe genus Commiphora, particularly the plant Commiphora mukul,especially as an agent with antiwrinkle activity. It further relates, byway of novel industrial products, to two particularly active productsisolated from these extracts, and to derivatives of these novelproducts.

It is known that the plant Commiphora mukul belongs to the family of theBurseraceae. Commiphora mukul is a plant of Indian origin which is verywidely used in traditional Indian medicine and in ayurvedic medicine. Aresin produced by Commiphora mukul, which is also called guggul, is usedin particular in these applications. This ayurvedic treatment was knownto comprise the treatment of obesity and lipidic disorders, as well asrheumatic diseases.

It should be noted that the term "guggul" denotes both the plant and theresin it produces. Also, this plant is a small tree or a shrub of 1.2 to1.8 m in height, which grows essentially in India, and the gum resin canbe harvested in the ordinary way by making an incision in the plant.

U.S. Pat. Nos. 4,847,071, 4,847,069, 4,946,671 and 4,954,332 haverecently described topical compositions, containing free radicalabsorbers and an anti-inflammatory agent, for protecting against UVradiation. Guggal or guggul extract is among the numerousanti-inflammatory agents mentioned.

Furthermore, document EP-A-513 671 has also disclosed compositionscontaining, as the active ingredient, a total lipophilic extract of theplant Commiphora mukul, which is obtained in particular from the resinof the bark of Commiphora mukul. This extract contains a high proportionof guggulsterones. This composition is described as having ananti-inflammatory, immunomodulating or antiandrogenic activity for thetreatment of acne and benign hypertrophy of the prostate.

SUMMARY OF THE INVENTION

It has now been discovered, surprisingly and unexpectedly, that extractsof a plant of the genus Commiphora, particularly the plant Commiphoramukul, have an antiwrinkle activity and can thus be used as cosmeticagents for improving the surface appearance of the skin and particularlyfor reducing the depth of large wrinkles and eliminating small wrinkles.

On the basis of this discovery, the Applicant carried out complementarysystematic studies aimed at identifying particularly active fractionsresponsible for this activity. It found in particular that thesefractions contained two novel products which were particularly active asregards the activity in question. These products could be isolated andtotally identified from extracts of the plant Commiphora mukul. Theytherefore constitute novel industrial products which have a remarkableactivity as cosmetic agents for combating wrinkles.

DETAILED DESCRIPTION OF THE INVENTION

The invention further relates to derivatives of the two novel productsisolated according to the invention.

Thus, according to a first aspect, the invention relates to the productsof formula (I): ##STR1## in which R is: a) a CH₂ OH group or

b) a COOH group,

and their salts or esters.

The invention relates very particularly, by way of novel industrialproducts, to the products of formula (II): ##STR2## in which R is: a) aCH₂ OH group, the product being denoted by formula II_(a),

b) a COOH group, the product being denoted by formula II_(b),

c) a group ##STR3## in which R₁ is a linear or branched alkyl groupcontaining from 1 to 6 carbon atoms, particularly the methyl group,

d) a group COOM, where M denotes an alkali metal, preferably sodium orpotassium, or a quaternary ammonium or amine group,

e) a group COOM'₀.5, where M' denotes an alkaline earth metal,preferably calcium, or

f) a group COOR₂, where R₂ denotes a linear or branched alkyl groupcontaining from 1 to 6 carbon atoms.

The invention relates very particularly to the two novel industrialproducts denoted respectively by II_(a) and II_(b) and having thefollowing formulae: ##STR4##

The two products could be isolated from the plant Commiphora mukul andwere completely identified by different analytical techniques, as willbecome apparent from the following description.

The product of formula II_(a), the empirical formula of which is C₃₀ H₅₀O₃, will be referred to as "commipherol". Its nomenclature is asfollows: (5R,10S,8R,9R)-3-oxopolypoda-13E,17E,21E-triene-8,30-diol.

The acid derivative of formula II_(b), the empirical formula of which isC₃₀ H₄₈ O₄, Will be referred to as "commipherin". This is(5R,10S,8R,9R)-8-hydroxy-3-oxopolypoda-13E,17E,21E-trien-30-oic acid.

The nomenclature used to denote the products of formulae II_(a) andII_(b) above is based on the name of the corresponding hydrocarbon; thisis the triterpene α-polypodatetraene, which is well known in theliterature, for example in the publication by Yoko Arai et al.,Tetrahedron Letters, (1992) 33 (10) 1325-8, relating to the plantPolypodiodes formosane. The carbon atoms are numbered as indicatedbelow: ##STR5##

It should be noted that various triterpene derivatives possessing thepolypodane carbon skeleton have been identified in other plants,particularly in ferns of the families of the Polypodiaceae, such asPolypodium vulgare, P. fauriei and P. virginianum (Y. Arai et al.,Phytochemistry, (1991) 30 (10) 3369 -3377; K. Shiojima et al.,Tetrahedron Lett., (1983) 24, 5733), the Aspidiaceae (M. Nishizawa etal., J. Chem. Soc., Chem. Commun. (1984) no. 7, 467-8) and theCheiropleuriaceae (R. Karnaya et al., Chem. Pharm. Bull. (1990) 38 (8)2130-2).

According to a second aspect, the invention further relates to processesfor the preparation of the two products II_(a) and II_(b) from the plantCommiphora mukul, as well as the acylation derivatives of the productII_(a), particularly the acetylation product, and the salts and estersof the product II_(b).

Different processes can be used to isolate the products of formulaeII_(a) and II_(b) from the plant Commiphora mukul.

In these processes, it is advantageous to start from the resin ofCommiphora mukul, which is subjected to different successive extractionand fractionation steps.

Thus, particularly advantageously, the resin of Commiphora mukul issubjected to a first so-called extraction step with a solvent or amixture of solvents, after which the extract is subjected to differentseparation steps for isolating a particularly active fraction containingat least one of the products of the invention.

The first extraction step can be carried out using a wide range ofsolvents of very different polarities.

The following may be mentioned, in order of increasing polarity, asexamples of solvents which can be used to carry out this step:

petroleum ether, with which 16% by weight of the crude resin can beextracted,

dichloromethane, with which 26% by weight of the crude resin can beextracted,

ethyl acetate, with which 30.5% by weight of the crude resin can beextracted,

ethanol, with which 26.5% by weight of the crude resin can be extracted.

FIG. 1 schematically represents different protocols for preparing theproducts of formulae II_(a) and II_(b) from an extract of the resin ofCommiphora mukul according to the invention.

According to the scheme of FIG. 1, a first extract according to theinvention, called extract G, is prepared from the resin of Commiphoramukul.

This extract G is obtained by extraction of the resin with 96% ethanolat 45° C. after grinding of the aggregates.

In a first step, the extract G is subjected to a series offractionations by high performance liquid chromatography. Each fractionis tested for its lipogenic activity on fibroblasts in culture using themethod explained below. These different fractionations ultimately yieldan active fraction, FIIB, whose characteristic peaks are identified onthe chromatogram.

More precisely, in this first step, the extract G will be subjectedinitially to a protocol B for isolating the most active fractions,whereby high performance liquid chromatography makes it possible toseparate the extract G into three fractions: F representing 92.5% of theextract G, FIII representing 4.5% of this extract, and FIV representing3%. The fraction FIII could be identified as consisting essentially ofsterols, and fraction FIV is composed essentially of the productsresulting from the rinsing of the chromatography column withdichloromethane.

The fraction F is then subjected to protocol C for separation by liquidchromatography, which yields two fractions called FI and FIIrespectively. The fraction FI, which is substantially inactive, isdiscarded. It represents 21.5% of F and consists essentially of sterones(Z- and E-guggulsterone).

The fraction FII, which has a lipogenic activity, is in turn subjectedto a fractionation by liquid chromatography, whereby it can be separatedinto three fractions: FIIA representing 19.5% of the extract G, FIIBrepresenting 20% of the extract G, and FIIC representing 31.5% of theextract G. The fraction FIIB is the most active of these threefractions. The positions of the corresponding peaks are identified onthe chromatogram.

It is then possible, in a second step, to obtain an active fractioncalled FIIB1, corresponding to the peaks of the fraction FIIB, directlyfrom the extract G by fractionation according to protocol E.

The two products of formulae II_(a) and II_(b) can then be separatedfrom the extract FIIB1 by preparative high performance liquidchromatography.

The two products II_(a) and II_(b), whose activities were found to besubstantially equivalent, were perfectly purified and could be isolatedby liquid chromatography under the following conditions:

Column: RP 18 Lichrospher 5 μm 125×4 mm

Mixtures: Water+0.1% CF₃ COOH Acetonitrile

UV detection: λ=210 nm

The product of formula II_(a) can then be subjected to a conventionalacylation step, particularly acetylation step, in order to prepare thecorresponding acylated derivatives, particularly the acetylatedderivative.

The product II_(b) can easily be converted to one of its salts,described above, by neutralization of the acid function at the end ofthe chain with a corresponding base.

Likewise, the esterification products of the product II_(b) may easilybe obtained by reacting it in conventional manner with a low molecularalcohol.

These reactions for acylating the product II_(a) or esterifying orsalifying the product II_(b) can also be carried out directly on amixture containing both the active products II_(a) and II_(b),particularly on the mixture FIIB1 described above.

For example, the acetylation of II_(a) with acetic anhydride can beeffected by treating the extract FIIB1 in the following manner: FIIB1 isdissolved in dichloromethane (1 volume), 1 volume of pyridine is added,followed by 1.2 equivalents of acetic anhydride per equivalent of FIIB1,and the reaction is allowed to proceed at room temperature overnight.

The Applicant found, totally surprisingly, that the extracts of theplant Commiphora mukul, especially the extracts particularly rich inproducts of formula II_(a) or II_(b), had a stimulating activity onlipogenesis inside the fibroblasts. This results in an increase in thecellular volume of the fibroblasts, leading to better contact with theextracellular protein network. This tones the dermis, making it possibleto reduce the depth of the large and small wrinkles and, consequently,to make them less obvious. This activity therefore enabled the Applicantto propose a particularly novel solution for improving the surfaceappearance of the skin.

Thus, according to a third aspect, the invention relates to the use ofat least one extract of a plant of the genus Commiphora, particularlythe plant Commiphora mukul, as a cosmetic agent for modifying thesurface of the skin by reducing the depth of the large and smallwrinkles to give the skin a smoother appearance.

Different extracts of the plant Commiphora mukul, particularly extractsrich in compounds of formula I, II, II_(a) or II_(b), in a mixturethereof or in derivatives of these products, as defined above, may beused in this application.

In a first variant, the gum resin called guggul may be used as theextract of the plant Commiphora mukul.

In another variant, an extract obtained after grinding of the aggregatesof the resin, followed by extraction with a solvent, is used as theextract of the plant Commiphora mukul. As seen above, a wide range ofsolvents may be used for this purpose.

However, referring to the classification of solvents by polarity, aspublished in particular by Veronika R. Meyer in PracticalHigh-performance Liquid Chromatography (1988), John Wiley & Sons, pp.120-121, solvents which will preferably be chosen are those whosepolarity parameter p' is less than 5.5 and preferably between 0.1 and4.5.

The above extract is advantageously obtained by extraction with anorganic solvent or a mixture of organic solvents selected from the groupconsisting of n-pentane, n-hexane, petroleum ether, cyclohexane,n-decane, dichloromethane, isopropanol, n-propanol, chloroform, ethanol,ethyl acetate, acetone and methanol.

In other variants of the invention, the extract may be made up ofdifferent products which share the characteristic of being enriched inat least one of the products of formula I or II, particularly of formulaII_(a) or II_(b), obtained from the extract described above.

As clearly illustrated in the examples given with reference to thescheme of FIG. 1, the products enriched in product(s) of the inventioncan be obtained for example from the extract G by subjecting thisextract to different successive separation steps, especially involvinghigh performance liquid chromatography or supercritical carbon dioxideextraction.

In one particularly advantageous variant of the invention, at least oneof the products of formula I or II, particularly of formula II_(a) orII_(b), will be used as the cosmetic agent for modifying the surface ofthe skin as indicated above.

According to a fourth aspect, the invention further relates to acomposition, in particular for cosmetic use, characterized in that itcontains at least one of the products of formula I or II, particularlyII_(a) or II_(b), or plant extracts containing at least one of theseproducts, particularly extracts of a plant of the genus Commiphora andvery particularly extracts of the plant Commiphora mukul, preferably incombination with an acceptable, in particular cosmetically acceptable,excipient or carrier.

Advantageously this composition contains from 0.001 to 1% by weight ofat least one of the products of formula (I) or (II), particularly(II_(a)) or (II_(b)), preferably from 0.01 to 0.1%.

Alternatively this composition very advantageously contains from 0.005to 5% by weight, preferably from 0.05 to 1% by weight, of an extract ofCommiphora mukul containing at least one of the above-mentionedproducts, particularly an extract of the resin of this plant.

The cosmetic compositions of the invention can be in different forms, inparticular in the form of solutions, milks, gels or creams.

In one variant of the invention, the cosmetic composition also containsa cosmetically effective amount of a product acting on fibronectinsynthesis and/or collagen synthesis.

Examples which may be mentioned of products acting on fibronectinsynthesis are galactolipids and particularly galactosylglycerides, theuse of which is described in the French patent application filed on Feb.15, 1995 under the number 95.01714, which has not yet been published.

Vitamin C may be mentioned as an example of a product acting on collagensynthesis.

The invention further relates to a method of cosmetic treatment formodifying the surface of the skin by reducing the depth of the large andsmall wrinkles to give the skin a smoother appearance, characterized inthat an effective amount of a product or a plant extract containing saidproduct is applied to the areas of skin to be treated, particularly tothe face, in order to obtain said surface modification, said product orsaid extract preferably being incorporated in a cosmetically acceptableexcipient.

In one variant of this method of cosmetic treatment, the above-mentionedplant extract is an extract of the plant Commiphora mukul.

Other characteristics and advantages of the invention will becomeapparent from the following Examples, which are given purely in order toillustrate the invention.

EXAMPLES Example 1

Preparation of the Extract G According to the Invention

This extract is prepared by extraction of the resin of Commiphora mukulafter grinding of the aggregates.

The extract is produced with 96% ethanol at 45° C. in the followingmanner: 10 g of resin and 200 ml of ethanol are introduced into a 500 mlround-bottomed flask fitted with a condenser and a stirrer and heated bymeans of a heating plate.

Stirring and extraction take a minimum of 2 h, but it is advisable toallow 4 to 5 h in order to improve the yield.

Extraction is followed by filtration and then by evaporation undervacuum.

The extraction yield is about 25% by weight.

Example 2

Preparation of the Fraction FIIB1 from the Extract G

This Example is given with reference to the scheme of FIG. 1. Table 1below gives details of protocols B, C, D and E as regards the nature andcharacteristics of the chromatography columns used, the type of detectorand the nature of the eluents used.

                  TABLE 1                                                         ______________________________________                                        Commiphora mukul                                                                    Product                                                                   to be    Fractions                                                            purified Column Detector Eluent obtained                                    ______________________________________                                        Protocol                                                                            extract kromasil 100 C18                                                                          220 mm methanol                                                                             F, FIII,                                B G 150 × 21.7 mm   FIV                                                   13 μm                                                                    Protocol fraction kromasil 100 C18 210 mm methanol/ FI, FII                   C F 150 × 21.7 mm  water                                                  13 μm  gradient                                                          Protocol fraction kromasil 100 C18 210 mm methanol/ FIIA,                     D FII 150 × 21.7 mm  water FIIB,                                          13 μm  gradient FIIC                                                     Protocol extract kromasil 100 C18 light methanol/ FIIB 1                      E G 150 × 21.7 mm scattering water                                        13 μm detector gradient                                                     (LSD)                                                                    ______________________________________                                    

Example 3

Preparation of the Products II_(a) and II_(b) from the Fraction FIIB 1

The two products II_(a) and II_(b) were separated by preparative liquidchromatography and purification on a C18 column using isocratic elutionby the recycling technique. The products II_(a) and II_(b) can bevisualized by detection at 210 nm.

The two products of formulae II_(a) and II_(b) were totally identifiedby mass spectrometry, which made it possible to verify the empiricalformulae established by NMR.

The results obtained by carbon NMR for the two products II_(a) andII_(b) are given in Tables 2 and 3 below:

                  TABLE 2                                                         ______________________________________                                        Chemical shifts of the different hydrocarbon groups of the product            II.sub.                                                                         Atom no.        .sup.13 C δ ppm                                                                  Multiplicity                                       ______________________________________                                         1            38.35    CH.sub.2                                                  2 34.02 CH.sub.2                                                              3 217.16  Cquat                                                               4 47.57 Cquat                                                                 5 55.18 CH                                                                    6 21.41 CH.sub.2                                                              7 43.80 CH.sub.2                                                              8 73.82 Cquat                                                                 9 60.36 CH                                                                   10 39.39 Cquat                                                                11 25.80 CH.sub.2                                                             12 31.20 CH.sub.2                                                             13 124.83  CH                                                                 14 135.47  Cquat                                                              15 39.34 CH.sub.2                                                             16 26.33 CH.sub.2                                                             17 124.54  CH                                                                 18 134.68  Cquat                                                              19 39.67 CH.sub.2                                                             20 26.16 CH.sub.2                                                             21 126.04  CH                                                                 22 134.71  Cquat                                                              23 21.41 CH.sub.3                                                             24 26.33 CH.sub.3                                                             25 14.89 CH.sub.3                                                             26 23.62 CH.sub.3                                                             27 16.06 CH.sub.3                                                             28 16.27 CH.sub.3                                                             29 13.77 CH.sub.3                                                             30 68.97 CH.sub.2                                                           ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                        Chemical shifts of the different hydrocarbon groups of the product            II.sub.                                                                         Atom no.        .sup.13 C δ ppm                                                                  Multiplicity                                       ______________________________________                                         1            38.35    CH.sub.2                                                  2 34.02 CH.sub.2                                                              3 217.10  Cquat                                                               4 47.57 Cquat                                                                 5 55.18 CH                                                                    6 21.35 CH.sub.2                                                              7 43.59 CH.sub.2                                                              8 74.54 Cquat                                                                 9 60.48 CH                                                                   10 39.39 Cquat                                                                11 25.85 CH.sub.2                                                             12 31.44 CH.sub.2                                                             13 125.15  CH                                                                 14 134.71  Cquat                                                              15 39.38 CH.sub.2                                                             16 26.28 CH.sub.2                                                             17 125.47  CH                                                                 18 134.55  Cquat                                                              19 38.03 CH.sub.2                                                             20 25.92 CH.sub.2                                                             21 143.82  CH                                                                 22 133.43  Cquat                                                              23 21.41 CH.sub.3                                                             24 26.33 CH.sub.3                                                             25 14.89 CH.sub.3                                                             26 23.54 CH.sub.3                                                             27 16.09 CH.sub.3                                                             28 15.88 CH.sub.3                                                             29 12.27 CH.sub.3                                                             30 171.14  Cquat                                                            ______________________________________                                    

Example 4 Supercritical CO₂ Extraction

Extraction is carried out in the following two steps on about 240 g ofground crude resin:

Step 1:

This step is performed in a conventional apparatus with pure CO₂ at 150bar and 40° C.

The CO₂ consumption is 2000 kg of CO₂ for 24 kg of resin to beextracted.

The extraction yield is about 12.50% based on the initial batch. Theextract obtained is discarded.

Step 2:

This step is performed in the same apparatus with a mixture containing98% by weight of 98% CO₂ and 2% by weight of ethanol.

1000 kg of CO₂ are used for 24 kg of crude resin (i.e. 18 kg of CO₂ for240 g of resin).

The extraction yield is about 10% based on the initial batch. This givesa so-called SFE (supercritical fluid extraction) enriched in moleculesII_(a) and II_(b) with a concentration factor of 6 to 8 relative to thecrude resin.

Example 5

Demonstration of the Activity of the Extracts and Products According tothe Invention

1. Culture

The cells used are 3T3 F442A, which constitute a line of murinepreadipocytes selected for their ability to convert to adipocytes if theculture conditions allow, in accordance with the method of Green, H. &Kehinde, C., Cell 1 (1974) 113.

This line actually constitutes a model for studying the differentiationof adipocytes in vitro.

As a monolayer during the multiplication phase, 3T3F442A have themorphology and enzymatic characteristics of fibroblasts.

The initially confluent cells cease to divide in order to enter theirearly differentiation phase. This differentiation leads to the formationof colonies of cells which undergo conversion to adipocytes.

This differentiation is accompanied by changes in the biosynthesis ofseveral proteins and by an increase in different enzymatic activities(acetyl CoA carboxylase, ATP citrate lyase, fatty acid synthetase,phosphoenolpyruvate kinase and glycero-3-phosphate dehydrogenase, calledG₃ PDH).

The aim was to measure the expression of two differentiation markers,namely glycero-3-phosphate dehydrogenase (G₃ PDH) on the one hand andcyclic AMP (cAMP) on the other.

It is pointed out here that the enzyme G₃ PDH allows the formation, inthe fibroblast, of glycerol 3-phosphate, a molecule which issubsequently involved in the synthesis of the intracellular lipids(triglycerides). Thus an increase in the activity of the G₃ PDH isdirectly linked to an increase in this synthesis.

Furthermore, it is known that the amount of cAMP, an intracellularmediator, increases during the intracellular lipolysis reaction. ThecAMP formed in the cell is then excreted thereby into the extracellularmedium. Thus a decrease in the cAMP content of the culture mediumrepresents a decrease in the degradation of the triglycerides and hencean intracellular accumulation of these lipids.

The resin of Commiphora mukul (extract G), the fraction FIIB1 and theproducts II_(a) and II_(b) were therefore studied with these twodifferentiation markers.

The fibroblasts are inoculated at the bottom of Petri dishes of diameter35 mm in Dulbecco's Modified Eagle's Medium (DMEM), in the presence of5% of calf serum (CS) and 5% of fetal calf serum (FCS). Each experimentis performed in triplicate.

During the treatment phase, the medium consists of DMEM+10% of fetalcalf serum.

The product or extract according to the invention is dissolved inethanol and used on the cultures at a final concentration of 5 μg/ml.

The culture operations are carried out as follows:

On day D=0: inoculation in DMEM+5% CS, 5% FCS

On day D+2: change of medium

On day D+5: treatment with resin of Commiphora mukul (extract G), FIIB1or II_(a) or II_(b) at 5 μg/ml in DMEM, 10% FCS

On day D+6: assay of cAMP in culture medium

On days D+7 and D+9: treatment identical to that performed on D+5

On day D+12: grinding of the cells for assay of G₃ PDH.

2. Assay of the Cyclic Adenosine 3,5-monophosphate (cAMP)

The assay of the cAMP, which is performed by radioimmunoassay or RIA(kit from Immunotech, a French Company, reference 1117), is based on theprinciple of antigen-antibody competition. The samples and standards areincubated, in the presence of cAMP radiolabeled with iodine 125, intubes where anti-cAMP antibodies have been fixed beforehand.

After incubation, the contents of the tubes are sucked out and theresidual radioactivity is counted with a gamma counter. A standard curveis prepared with 6 known concentrations of cAMP and the concentration ofthe samples is defined by means of this calibration curve.

As the cAMP is produced and excreted by the cells, one is thereforemeasuring the cAMP contained in the culture medium. More precisely, oneis measuring the amount of cAMP excreted into the culture medium in 24hours.

3. Determination of the glycero-3-phosphate dehydrogenase (G₃ PDH)Activity

The cellular monolayer is recovered by scraping and vigorouslyhomogenized in TRIS-HCl buffer (25 mM, pH 7.4), 1 mM EDTA, at 4° C. TheG₃ PDH activity is determined on the supernatant of the ground cellularmaterial immediately after centrifugation.

G₃ PDH catalyzes the following reaction: ##EQU1##

The conversion of the coenzyme NADH (hydrogenated nicotinamide adeninedinucleotide) to NAD as a function of time, which represents the rate ofthe enzymatic reaction and hence the activity of the enzyme G₃ PDH, ismeasured by spectrophotometry at 340 nm.

It is possible to calculate an absorption difference (ΔAbs)/min, whichcorresponds to the initial rate of the enzymatic reaction.

The results are expressed in terms of specific activity, i.e. in nmol ofNADH converted/min/mg of cellular proteins (the total cellular proteincontent is evaluated by the method of BCA-PIERCE: protein assayreagent).

4.1. G₃ PDH Activity

The experimental results of the evaluation of the activity of the enzymeG₃ PDH are shown in Table 4 below.

The activity A₁ of the products according to the invention onstimulation of the activity of this enzyme is calculated according tothe following formula: ##EQU2## in which: V_(p) is the mean value, overthe three experiments, of the rate of conversion of NADH, expressed innmol/min/mg of cellular proteins, in the cultures treated with theproducts according to the invention,

V_(t) is the mean value of this rate in the control cultures.

                  TABLE 4                                                         ______________________________________                                                     Rate of conversion of NADH                                                                     Activity                                          Cultures nmol/min/mg of proteins A.sub.1 %                                  ______________________________________                                        Control cultures                                                                            49.6 ± 3.39   0                                                Extract G 156 ± 43 215                                                     Fraction FIIB 1 242 ± 42 394                                               II.sub.a 222 ± 88 348                                                      II.sub.b 352 ± 62 610                                                    ______________________________________                                    

It is therefore very clear from Table 4 that the products according tothe invention, whether they be the extract G, the fraction FIIB1 or theproducts II_(a) or II_(b), very greatly increase the activity of theenzyme G₃ PDH in the fibroblast cultures, compared with the activity ofthis enzyme in the control cultures. In fact, it is seen that theactivity of this enzyme is increased 3-fold by the action of the extractG and 7-fold by the action of the compound II_(b). Thus it isdemonstrated that the products according to the invention contribute toa substantial increase in the synthesis of intracellular triglycerides.

4.2. Assay of cAMP

The quantity of cAMP excreted in 24 hours into the medium of thedifferent cultures prepared is shown in Table 5. It is expressed innmol/liter of medium. The activity A₂ of the products according to theinvention on the excretion of cAMP by the cells, which is directlyrelated to the intracellular lipolysis reaction, is calculated accordingto the following formula: ##EQU3## in which: q_(p) represents the meanquantity, over the three experiments, of cAMP excreted into the mediumof the cultures treated with the products according to the invention,expressed in nmol/liter/24 hours,

q_(t) represents this mean quantity in the case of the control cultures.

                  TABLE 5                                                         ______________________________________                                                       cAMP excreted                                                    Cultures nmol/liter/24 hours A                                                                          .sub.2 %                                          ______________________________________                                        Control cultures                                                                               66 ± 3.5                                                                              0                                                   Extract G 56.8 ± 3.8 -13.9                                                 FIIB 1 42 ± 2 -36.4                                                      ______________________________________                                    

These results given in Table 5 show that the quantity of cAMP excretedinto the culture medium is smaller in the case of the cultures treatedwith the products of the invention than in the case of the controlcultures.

Thus, in the cells of the treated cultures, it is apparent that thelipolysis is very considerably reduced compared with that which occursin the cells of the control cultures.

In conclusion, these experiments clearly demonstrate that the productsaccording to the invention act via two complementary routes to increasethe quantity of intracellular lipids, on the one hand by favoring theirsynthesis, which is demonstrated by the increase in the activity of theenzyme G₃ PDH, and on the other hand by limiting their degradation,which is demonstrated by the reduction in the cAMP content of thetreated cultures.

It will moreover be observed that the two molecules II_(a) and II_(b)give the best results and in fact appear to be the basis of thelipogenic activity of the extracts and fractions according to theinvention.

Thus the products according to the invention accelerate thedifferentiation of the adipocytes in the fibroblasts. Furthermore,because of the accumulation of the lipids, these cells increase involume and thus allow better contact with the extracellular proteinnetwork, thereby consolidating the dermis. The result of this tonicityof the dermis is to decrease the depth of the large and small wrinklesand give the surface of the skin a smoother appearance.

Example 6

Antiwrinkle Cream

An antiwrinkle cream is prepared by mixing the constituents below, givenwith their percentages by weight based on the final composition, inaccordance with the following preparative protocol:

A mixture A consisting of:______________________________________Brij 72® 0.8 Brij 721 ® 2.2 Tegin 90 ® 1.7 Stearyl alcohol 1.8 Stearine 3.0Silicone oil (Fluid 200 ®) 0.20 Squalane 10.0 Miglyol 812 ® 10.0D,L-α-Tocopherol acetate 0.2 Phenonip 0.5 SFE of Example 40.5______________________________________

is prepared.

A mixture B consisting of:______________________________________B:Glycerol 5.00 Water 58.53 Carbopol 940 0.20 is added and then C, D and Econsisting respectively of: C: 10% sodium hydroxide solution 0.07 D:Wheat proteins 5.00 E: Perfume0.30______________________________________

are added.

Example 7

Eye Contour Gel with Antiwrinkle Activity

A composition is prepared by mixing the components A, B, C, D and Ebelow, the constituents of which are given with their percentages byweight based on the finalcomposition.______________________________________A: Carbopol 1342 ®0.40 Water 83.20 B: 10% sodium hydroxide solution 0.40 C: Product II_(a)according to the invention 0.1 Miglyol 829 ® 10.00 Phenonip 0.50D,L-α:-Tocopherol acetate 0.20 D: Wheat proteins 5.00 E: Perfume0.20______________________________________

We claim:
 1. Product of formula (I): ##STR6## in which R is: a) a CH₂ OHgroup orb) a COOH group, and salts and esters thereof.
 2. Productaccording to claim 1 of formula (II): ##STR7## in which R is: a) a CH₂OH group, the product being denoted by formula II_(a).b) a COOH group,the product being denoted by formula II_(b), c) a group ##STR8## inwhich R₁ is a linear or branched alkyl group having from 1 to 6 carbonatoms, d) a group COOM, where M denotes an alkali metal, e) a groupCOOM'₀.5, where M' denotes an alkaline earth metal, or f) a group COOR₂where R₂ denotes a linear or branched alkyl group having from 1 to 6carbon atoms.
 3. Product according to claim 2, having a formula (II)_(a): ##STR9##
 4. Product according to claim 2, having a formula (II_(b)):5. Process for the preparation of a product as defined in claim 1,comprising the steps of treating resin of Commiphora mukul by extractionwith an organic solvent to prepare an extract designated extract G,subjecting said extract G to at least one fractionation step in order toisolate a fraction consisting essentially of at least one productselected from the group consisting of the product of formula II_(a) theproduct of formula II_(b) ##STR10## and mixtures thereof, and,optionally forming a salt from or esterifying the product II_(b).
 6. Theprocess according to claim 5, wherein the solvent used to perform theextraction has a solubility parameter p' which is less than 5.5.
 7. Theprocess according to claim 6, wherein the solvent used to perform theextraction is selected from the group consisting of n-pentane, n-hexane,petroleum ether, cyclohexane, n-decane, dichloromethane, isopropanol,n-propanol, chloroform, ethanol, ethyl acetate, acetone and methanol. 8.A method for modifying the surface of the skin by reducing the depth oflarge and small wrinkles to give the skin a smoother appearance,comprising application to an area of the skin to be treated of acosmetic composition containing an effective amount of at least oneproduct of formula (I): ##STR11## in which R is: a) a CH₂ OH group orb)a COOH group, and salts and esters thereof.
 9. The method according toclaim 8, wherein said cosmetic composition contains at least one productof formula (II): ##STR12## in which R is: a) a CH₂ OH group, the productbeing denoted by formula II_(a).b) a COOH group, the product beingdenoted by formula II_(b), c) a group ##STR13## in which R₁ is a linearor branched alkyl group containing from 1 to 6 carbon atoms, d) a groupCOOM, where M denotes an alkali metal, e) a group COOM'₀.51, where M'denotes an alkaline earth metal, or f) a group COOR₂, where R₂ denotes alinear or branched alkyl group containing from 1 to 6 carbon atoms. 10.The method according to claim 8, wherein said cosmetic compositioncomprises a product of formula (II_(a)): ##STR14##
 11. The methodaccording to claim 8, wherein said cosmetic composition comprises aproduct of formula (II_(b)):
 12. The method according to claim 8,wherein said cosmetic composition contains from 0.001 to 1% by weight ofsaid product of formula (I).
 13. The method according to claim 8,wherein said cosmetic composition further contains a product forimproving fibronectin synthesis.
 14. The method according to claim 8,wherein said cosmetic composition further contains a product forimproving collagen synthesis.